ArticleEMBO molecular medicine2015
Regulation of hematogenous tumor metastasis by acid sphingomyelinase.
Article in EMBO molecular medicine, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
47 citing papers in PubMed, 83 citations in OpenAlex.
- Potential Mechanisms of Platelet Dysfunction and Bleeding in Acid Sphingomyelinase Deficiency.Cells · 2026Review
- Platelet‑circulating tumor cell crosstalk: A pivotal target in cancer diagnosis and therapy (Review).Oncology reports · 2026Review
- The role of platelets in cancer: from their influence on tumor progression to their potential use in liquid biopsy.Biomarker research · 2025Review
- Advances in ORMDL Research in Malignant Tumors: A Review.OncoTargets and therapy · 2025Review
- A Novel Systemic siDR6 Delivery System Based on DP7-C for the Treatment of Metastatic Lung Cancer.International journal of nanomedicine · 2025Article
- Sphingolipid metabolism and regulated cell death in malignant melanoma.Apoptosis : an international journal on programmed cell death · 2024Review
- Article
- Expression and prognostic role of sphingosine 1-phosphate receptor 4 (S1PR4) as a biomarker of skin cutaneous melanoma.Heliyon · 2024Article
- Low-intensity exercise training improves systolic function of heart during metastatic melanoma-induced cachexia in mice.Heliyon · 2024Article
- The dynamic role of platelets in cancer progression and their therapeutic implications.Nature reviews. Cancer · 2024Review
- Transcriptome and Lipidomic Analysis Suggests Lipid Metabolism Reprogramming and UpregulatingMetabolites · 2023Article
- The critical role of platelet in cancer progression and metastasis.European journal of medical research · 2023Review
- Ceramide as an endothelial cell surface receptor and a lung-specific lipid vascular target for circulating ligands.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Mass Spectrometry Detects Sphingolipid Metabolites for Discovery of New Strategy for Cancer Therapy from the Aspect of Programmed Cell Death.Metabolites · 2023Review
- Tumor educated platelet: the novel BioSource for cancer detection.Cancer cell international · 2023Review
- Epigenetic Regulation Mediated by Sphingolipids in Cancer.International journal of molecular sciences · 2023Review
- Review
- The acid sphingomyelinase/ceramide system in COVID-19.Molecular psychiatry · 2022Review
- Sphingolipid metabolism in the development and progression of cancer: one cancer's help is another's hindrance.Molecular oncology · 2021Review
- Ceramide Metabolism Enzymes-Therapeutic Targets against Cancer.Medicina (Kaunas, Lithuania) · 2021Review
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Authors and funding
14 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Metastatic dissemination of cancer cells is the ultimate hallmark of malignancy and accounts for approximately 90% of human cancer deaths. We investigated the role of acid sphingomyelinase (Asm) in the hematogenous metastasis of melanoma cells. Intravenous injection of B16F10 melanoma cells into wild-type mice resulted in multiple lung metastases, while Asm-deficient mice (Smpd1(-/-) mice) were protected from pulmonary tumor spread. Transplanting wild-type platelets into Asm-deficient mice reinstated tumor metastasis. Likewise, Asm-deficient mice were protected from hematogenous MT/ret melanoma metastasis to the spleen in a mouse model of spontaneous tumor metastasis. Human and mouse melanoma cells triggered activation and release of platelet secretory Asm, in turn leading to ceramide formation, clustering, and activation of α5β1 integrins on melanoma cells finally leading to adhesion of the tumor cells. Clustering of integrins by applying purified Asm or C16 ceramide to B16F10 melanoma cells before intravenous injection restored trapping of tumor cells in the lung in Asm-deficient mice. This effect was revertable by arginine-glycine-aspartic acid peptides, which are known inhibitors of integrins, and by antibodies neutralizing β1 integrins. These findings indicate that melanoma cells employ platelet-derived Asm for adhesion and metastasis.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.